A Live Attenuated Dengue Virus Vaccine (Dengvaxia) is Suppressed in Individuals with Immunity to Serotype 4
Cameron Adams, Lindsay D Hein, Laura J White, Ruby Shah, Lakshmanane Premkumar, Jedas Veronica Daag, Kristal An Agrupis, Maria Vinna Crisostomo, Michelle Ylade, Jacqueline Deen, Ana Lena Lopez, Aravinda M de SilvaAbstract
Background
Dengvaxia® was the first live attenuated tetravalent dengue virus (DENV) vaccine to be tested and approved for use in people. While Dengvaxia was designed to be tetravalent, in humans, the vaccine performed like a monovalent DENV4 vaccine because the DENV4 vaccine virus replicated better than other vaccine serotypes. Dengvaxia® was safe and efficacious in children who were DENV-immune at baseline and contraindicated for use in DENV-naïve children.
Methods
When Dengvaxia® was rolled out as a pediatric vaccine in the Philippines in 2016, we established a prospective cohort to assess vaccine performance by baseline dengue serostatus. Here we report on how baseline monotypic immunity to each serotype (reflecting one past DENV infection) impacted Dengvaxia® responses.
Results
We observed that in children with baseline immunity to DENV1, 2 or 3, the vaccine stimulated a secondary serotype cross-neutralizing Ab response, which likely explains the overall favorable performance of the vaccine in seropositive children enrolled in phase 3 trials. We observed a high frequency (61%) of vaccine suppression among DENV4 monotypic immune children.
Conclusions
Our results confirm the replication dominance of the DENV4 vaccine component in Dengvaxia® and directly implicate pre-existing DENV4 immunity in the suppression of the vaccine. Our results have broader implications for evaluating the performance of other DENV vaccines in seropositive individuals.